Autism-Associated DNA Methylation at Birth from Multiple Tissues Is Enriched for Autism Genes in the Early Autism Risk Longitudinal Investigation (EARLI)

Poster Presentation
Saturday, May 12, 2018: 11:30 AM-1:30 PM
Hall Grote Zaal (de Doelen ICC Rotterdam)
K. M. Bakulski1, M. D. Fallin2, A. P. Feinberg3, J. I. Feinberg2, I. Hertz-Picciotto4, L. A. Croen5, C. J. Newschaffer6, S. Brown3, J. Dou7 and M. Aung7, (1)University of Michigan, Ann Arbor, MI, (2)Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, (3)Johns Hopkins University, Baltimore, MD, (4)University of California at Davis, Davis, CA, (5)Division of Research, Kaiser Permanente, Oakland, CA, (6)AJ Drexel Autism Institute, Philadelphia, PA, (7)University of Michigan, School of Public Health, Ann Arbor, MI
Background: Risk for autism spectrum disorders (ASD) is conferred through genetic and environmental exposures, and emerging evidence suggests DNA methylation is altered in ASD. Few studies have considered prospective designs with DNA methylation measured in multiple tissues.

Objectives: To determine the relationships between DNA methylation in maternal blood, cord blood, and placenta with ASD diagnosis.

Methods: In the Early Autism Risk Longitudinal Investigation (EARLI), an ASD-enriched birth cohort, genome-scale maternal blood (early n=140 and late n=75 pregnancy), infant cord blood (n=141), and placenta (maternal n=106 and fetal n=107 compartments) DNA methylation was assessed on the Illumina 450k HumanMethylation array and compared to ASD diagnosis at 36 months of age. We tested for differences in site-specific and global methylation and for enrichment of single sites for ASD risk genes from the Simons Foundation Autism Research Initiative (SFARI) database.

Results: No individual DNA methylation site was associated at genome-wide significance, however individual DNA methylation sites associated with ASD (P<0.05) in each tissue were highly enriched for SFARI genes (cord blood P = 2.6x10-30, maternal blood early pregnancy P = 1.6x10-29, maternal blood late pregnancy P= 4.1x10-12, maternal placenta P= 2.4x10-27, fetal placenta P=1.2x10-13). Analyses of additional behavioral phenotypes will be presented, as well as results for overall (global) methylation comparisons across cord, maternal blood, and placenta.

Conclusions: Across multiple tissues, DNA methylation sites nominally associated with later ASD diagnosis were enriched for ASD risk genes. Our blood and placenta tissue study demonstrates the utility of examining DNA methylation prior to ASD diagnosis.

See more of: Epidemiology
See more of: Epidemiology